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Title: insoluble proteins catch heterologous soluble proteins into inclusion bodies by intermolecular interaction of aggregating peptides

Authors
  • Carratalá, Jose Vicente1, 1, 2
  • Cisneros, Andrés1, 1
  • Hellman, Elijah1, 1
  • Villaverde, Antonio1, 1, 2
  • Ferrer-Miralles, Neus1, 1, 2
  • 1 Autonomous University of Barcelona, Bellaterra, Barcelona, 08193, Spain , Bellaterra (Spain)
  • 2 Bioengineering, Biomaterials and Nanomedicine Networking Biomedical Research Centre (CIBER-BBN), Bellaterra, Barcelona, 08193, Spain , Bellaterra (Spain)
Type
Published Article
Journal
Microbial Cell Factories
Publisher
BioMed Central
Publication Date
Feb 02, 2021
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12934-021-01524-3
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundProtein aggregation is a biological event observed in expression systems in which the recombinant protein is produced under stressful conditions surpassing the homeostasis of the protein quality control system. In addition, protein aggregation is also related to conformational diseases in animals as transmissible prion diseases or non-transmissible neurodegenerative diseases including Alzheimer, Parkinson’s disease, amyloidosis and multiple system atrophy among others. At the molecular level, the presence of aggregation-prone domains in protein molecules act as seeding igniters to induce the accumulation of protein molecules in protease-resistant clusters by intermolecular interactions.Results In this work we have studied the aggregating-prone performance of a small peptide (L6K2) with additional antimicrobial activity and we have elucidated the relevance of the accompanying scaffold protein to enhance the aggregating profile of the fusion protein. Furthermore, we demonstrated that the fusion of L6K2 to highly soluble recombinant proteins directs the protein to inclusion bodies (IBs) in E. coli through stereospecific interactions in the presence of an insoluble protein displaying the same aggregating-prone peptide (APP).ConclusionsThese data suggest that the molecular bases of protein aggregation are related to the net balance of protein aggregation potential and not only to the presence of APPs. This is then presented as a generic platform to generate hybrid protein aggregates in microbial cell factories for biopharmaceutical and biotechnological applications.

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